Abstract
Approximately 30% of patients treated with radical prostatectomy (RP) for prostate cancers experience biochemical recurrence (BCR). Post-operative radiation therapy (RT) can be either offered immediately after the surgery in case of aggressive pathological features or proposed early if BCR occurs. Until recently, little data were available regarding the optimal RT timing, protocol, volumes to treat, and the benefit of adding androgen deprivation therapies to post-operative RT. In this review, we aim to pragmatically discuss current literature data on these points. Early salvage RT appears to be the optimal post-operative approach, improving oncological outcomes especially with low prostate-specific antigen (PSA) levels, as well as sparing several unnecessary adjuvant treatments. The standard RT dose is still 64–66 Gy to the prostate bed in conventional fractionation, but hypofractionation protocols are emerging pending on late toxicity data. Several scientific societies have published contouring atlases, even though they are heterogeneous and deserve future consensus. During salvage RT, the inclusion of pelvic lymph nodes is also controversial, but preliminary data show a possible benefit for PSA > 0.34 ng/ml at the cost of increased hematological side effects. Concomitant ADT and its duration are also discussed, possibly advantageous (at least in terms of metastasis-free survival) for PSA rates over 0.6 ng/ml, taking into account life expectancy and cardiovascular comorbidities. Intensified regimens, for instance, with new-generation hormone therapies, could further improve outcomes in carefully selected patients. Finally, recent advances in molecular imaging, as well as upcoming breakthroughs in genomics and artificial intelligence tools, could soon reshuffle the cards of the current therapeutic strategy.
Highlights
Radical prostatectomy (RP) is one of the standard treatment options for localized prostate cancers (PCa)
Hormone therapy acts as a radiosensitizer, disabling androgen receptor-mediated reparation of DNA damages caused by radiation therapy (RT) in PCa cells, decreasing the ability of cancer cells to recover from radiation damages [50]
ANZUP1801 is exploring the addition of 96 weeks of darolutamide to RT and androgen deprivation therapy (ADT), either for primary definitive therapy or in an adjuvant setting for very high-risk PCa (NCT04136353), and STEEL is studying the addition of 2 years of Enzalutamide with salvage RT and 2 years of ADT when aggressive features are displayed (NCT03809000)
Summary
Radical prostatectomy (RP) is one of the standard treatment options for localized prostate cancers (PCa). Metastasis-free survival (MFS) and overall survival (OS), were improved only in the SWOG8794 trial These studies offer long-term follow-ups, but salvage RT at the time of biological recurrence was not compulsory in the control arm, and, when offered [6], was often late, at a high PSA level (PSA > 0.5 ng/ml). Up to 40% of patients eligible to adjuvant RT according to the inclusion criteria of these trials did not present BCR after 10 years, theoretically not needing further treatments [3, 4] For some of these patients, adjuvant RT could have even been an overtreatment, associated with respectively 15%–35% and 2%– 8% early and late grade 2 or higher genito-urinary (GU) and gastro-intestinal (GI) toxicity [4,5,6].
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